PMID- 12665511
OWN - NLM
STAT- MEDLINE
DCOM- 20030710
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 22
DP  - 2003 May 30
TI  - Two motifs in the translational repressor PHAS-I required for efficient 
      phosphorylation by mammalian target of rapamycin and for recognition by raptor.
PG  - 19667-73
AB  - Mammalian target of rapamycin (mTOR) is the central element of a signaling 
      pathway involved in the control of mRNA translation and cell growth. The actions 
      of mTOR are mediated in part through the phosphorylation of the eukaryotic 
      initiation factor 4E-binding protein, PHAS-I. In vitro mTOR phosphorylates PHAS-I 
      in sites that control PHAS-I binding to eukaryotic initiation factor 4E; however, 
      whether mTOR directly phosphorylates PHAS-I in cells has been a point of debate. 
      The Arg-Ala-Ile-Pro (RAIP motif) and Phe-Glu-Met-Asp-Ile (tor signaling motif) 
      sequences found in the NH2- and COOH-terminal regions of PHAS-I, respectively, 
      are required for the efficient phosphorylation of PHAS-I in cells. Here we show 
      that mutations in either motif markedly decreased the phosphorylation of 
      recombinant PHAS-I by mTOR in vitro. Wild-type PHAS-I, but none of the mutant 
      proteins, was coimmunoprecipitated with hemagglutinin-tagged raptor, an 
      mTOR-associated protein, after extracts of cells overexpressing raptor had been 
      supplemented with recombinant PHAS-I proteins. Moreover, raptor overexpression 
      enhanced the phosphorylation of wild-type PHAS-I by mTOR but not the 
      phosphorylation of the mutant proteins. The results not only provide direct 
      evidence that both the RAIP and tor signaling motifs are important for the 
      phosphorylation by mTOR, possibly by allowing PHAS-I binding to raptor, but also 
      support the view that mTOR phosphorylates PHAS-I in cells.
FAU - Choi, Kin Man
AU  - Choi KM
AD  - Department of Pharmacology, University of Virginia School of Medicine, 
      Charlottesville 22908, USA.
FAU - McMahon, Lloyd P
AU  - McMahon LP
FAU - Lawrence, John C Jr
AU  - Lawrence JC Jr
LA  - eng
GR  - DK28312/DK/NIDDK NIH HHS/United States
GR  - DK52753/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030328
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (RPTOR protein, human)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, rat)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Carrier Proteins/chemistry/genetics/*metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/chemistry/genetics/*metabolism
MH  - Phosphoproteins/chemistry/genetics/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinases/genetics/*metabolism
MH  - Proteins/genetics/*metabolism
MH  - Rats
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Regulatory-Associated Protein of mTOR
MH  - TOR Serine-Threonine Kinases
EDAT- 2003/04/01 05:00
MHDA- 2003/07/11 05:00
CRDT- 2003/04/01 05:00
PHST- 2003/04/01 05:00 [pubmed]
PHST- 2003/07/11 05:00 [medline]
PHST- 2003/04/01 05:00 [entrez]
AID - S0021-9258(20)79983-7 [pii]
AID - 10.1074/jbc.M301142200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 May 30;278(22):19667-73. doi: 10.1074/jbc.M301142200. Epub 2003 
      Mar 28.